Auditory-motor mapping training as an intervention to facilitate speech output in non-verbal children with autism: a proof of concept study

Although up to 25% of children with autism are non-verbal, there are very few interventions that can reliably produce significant improvements in speech output. Recently, a novel intervention called Auditory-Motor Mapping Training (AMMT) has been developed, which aims to promote speech production directly by training the association between sounds and articulatory actions using intonation and bimanual motor activities. AMMT capitalizes on the inherent musical strengths of children with autism, and offers activities that they intrinsically enjoy. It also engages and potentially stimulates a network of brain regions that may be dysfunctional in autism. Here, we report an initial efficacy study to provide 'proof of concept' for AMMT. Six non-verbal children with autism participated. Prior to treatment, the children had no intelligible words. They each received 40 individual sessions of AMMT 5 times per week, over an 8-week period. Probe assessments were conducted periodically during baseline, therapy, and follow-up sessions. After therapy, all children showed significant improvements in their ability to articulate words and phrases, with generalization to items that were not practiced during therapy sessions. Because these children had no or minimal vocal output prior to treatment, the acquisition of speech sounds and word approximations through AMMT represents a critical step in expressive language development in children with autism.     

Pet Dogs Improve Family Functioning and Reduce Anxiety in Children with Autism Spectrum Disorder

ABSTRACT

There is increasing evidence to suggest that dogs are beneficial for children with Autism Spectrum Disorder (ASD) in therapy sessions, and anecdotal reports suggest that dogs may have wider benefits, in a family setting. This study investigated the effect of dog ownership on family functioning and child anxiety. Using a validated scale of family strengths and weaknesses (Brief Version of the Family Assessment Measure-III [General Scale]), we compared parents of children with ASD who had recently acquired a pet dog (n=42, Intervention group) with a similar group of parents not acquiring a dog (n=28, Control group) at matched time points. A sub-population (n =14 acquiring a dog, n=26 controls) completed a parental-report measure of child anxiety (Spence Children's Anxiety Scale). The primary carer completed the scales via telephone at Baseline (up to 17 weeks before acquiring a dog), Post-intervention (3–10 weeks after acquisition), and Follow-up (25–40 weeks after acquisition). Over time, scores for family functioning showed significant improvements (reduced family weaknesses, increased strengths) in the dog-owning compared with the non-dog owning group. In comparison with the non-dog owning group, anxiety scores in the dog-owning group reduced by a greater percentage, most notably in the domains of Obsessive Compulsive Disorder (26% greater decrease), Panic Attack and Agoraphobia (24%), Social Phobia (22%), and Separation Anxiety (22%). The results illustrate the potential of pet dogs to improve whole family functioning and child anxiety.     

Social Effects of a Dog's Presence on Children with Disabilities

ABSTRACT

Productive and positive interactions between dogs and humans have been documented in studies using dogs trained as companion animals and as assistants for people with disabilities. In this study, the effects of the presence of a dog on social interactions between three 5–9-year-old children with developmental disabilities and their teacher at an elementary school were analyzed. A single-case experimental design with repeated measures and with replicated effects across participants was employed to assess changes in interactions from baseline to an intervention condition. During baseline, interactions were assessed in the social environment of a room adjacent to the classroom, which had a toy dog and other play materials, during time with the teacher. The experimental change introduced sequentially and systematically across the participants was the additional presence of an obedience-trained dog, a German Shepherd/Labrador Retriever cross. Interactions between the children and their teacher were examined during morning sessions using reliable direct observation interval recording procedures. All participants demonstrated an increase in overall positive initiated behaviors (verbal and non-verbal) toward both the teacher and the dog. The children also showed an overall decrease in negative initiated behaviors. In addition, observational ratings showed positive generalization of improved social responsiveness by the children in their classroom following the completion of the experimental sessions. This study supports the position that children with developmental disabilities benefit from the use of skilled dogs as teaching assistants and therapeutic adjuncts.     

Prefrontal Neuromodulation Using rTMS Improves Error Monitoring and Correction Function in Autism

One important executive function known to be compromised in autism spectrum disorder (ASD) is related to response error monitoring and post-error response correction. Several reports indicate that children with ASD show reduced error processing and deficient behavioral correction after an error is committed. Error sensitivity can be readily examined by measuring event-related potentials (ERP) associated with responses to errors, the fronto-central error-related negativity (ERN), and the error-related positivity (Pe). The goal of our study was to investigate whether reaction time (RT), error rate, post-error RT change, ERN, and Pe will show positive changes following 12-week long slow frequency repetitive TMS (rTMS) over dorsolateral prefrontal cortex (DLPFC) in high functioning children with ASD. We hypothesized that 12 sessions of 1 Hz rTMS bilaterally applied over the DLPFC will result in improvements reflected in both behavioral and ERP measures. Participants were randomly assigned to either active rTMS treatment or wait-list (WTL) groups. Baseline and post-TMS/or WTL EEG was collected using 128 channel EEG system. The task involved the recognition of a specific illusory shape, in this case a square or triangle, created by three or four inducer disks. ERN in TMS treatment group became significantly more negative. The number of omission errors decreased post-TMS. The RT did not change, but post-error RT became slower. There were no changes in RT, error rate, post-error RT slowing, nor in ERN/Pe measures in the wait-list group. Our results show significant post-TMS differences in the response-locked ERP such as ERN, as well as behavioral response monitoring measures indicative of improved error monitoring and correction function. The ERN and Pe, along with behavioral performance measures, can be used as functional outcome measures to assess the effectiveness of neuromodulation (e.g., rTMS) in children with autism and thus may have important practical implications.     

Intelligence May Moderate the Cognitive Profile of Patients with ASD

BackgroundThe intelligence of individuals with Autism Spectrum Disorder (ASD) varies considerably. The pattern of cognitive deficits associated with ASD may differ depending on intelligence. We aimed to study the absolute and relative severity of cognitive deficits in participants with ASD in relation to IQ.MethodsA total of 274 children (M age = 12.1, 68.6% boys) participated: 30 ASD and 22 controls in the below average Intelligence Quotient (IQ) group (IQ<85), 57 ASD and 54 controls in the average IQ group (85<IQ<115) and 41 ASD and 70 controls in the above average IQ group (IQ>115). Matching for age, sex, Full Scale IQ (FSIQ), Verbal IQ (VIQ), Performance IQ (PIQ) and VIQ-PIQ difference was performed. Speed and accuracy of social cognition, executive functioning, visual pattern recognition and basic processing speed were examined per domain and as a composite score.ResultsThe composite score revealed a trend significant IQ by ASD interaction (significant when excluding the average IQ group). In absolute terms, participants with below average IQs performed poorest (regardless of diagnosis). However, in relative terms, above average intelligent participants with ASD showed the most substantial cognitive problems (particularly for social cognition, visual pattern recognition and verbal working memory) since this group differed significantly from the IQ-matched control group (p < .001), whereas this was not the case for below-average intelligence participants with ASD (p = .57).ConclusionsIn relative terms, cognitive deficits appear somewhat more severe in individuals with ASD and above average IQs compared to the below average IQ patients with ASD. Even though high IQ ASD individuals enjoy a certain protection from their higher IQ, they clearly demonstrate cognitive impairments that may be targeted in clinical assessment and treatment. Conversely, even though in absolute terms ASD patients with below average IQs were clearly more impaired than ASD patients with average to above average IQs, the differences in cognitive functioning between participants with and without ASD on the lower end of the IQ spectrum were less pronounced. Clinically this may imply that cognitive assessment and training of cognitive skills in below average intelligent children with ASD may be a less fruitful endeavour. These findings tentatively suggest that intelligence may act as a moderator in the cognitive presentation of ASD, with qualitatively different cognitive processes affected in patients at the high and low end of the IQ spectrum.     

对比分析间歇正压通气与无创高频振荡通气分别联合微创肺表面活性物质治疗新生儿呼吸窘迫综合征疗效及安全性

摘要 目的：对比经鼻间歇正压通气（NIPPV）与无创高频振荡通气（nHFOV）分别联合微创肺表面活性物质（PS）治疗新生儿呼吸窘迫综合征（RDS）的临床效果及安全性。方法：选择2019年1月至2021年12月我院新生儿科收治的100例RDS患儿作为研究对象,采用随机数字表法分为对照组和观察组,各50例。对照组新生儿采用NIPPV联合微创PS治疗,观察组新生儿采用nHFOV联合微创PS治疗。比较两组患儿治疗相关指标（机械通气时间、氧暴露时间、住院天数）、临床症状（吸气三凹征、进行性呼吸困难、气促）改善时间、血气指标[脉血氧分压（PaO₂）、动脉血二氧化碳分压（PaCO₂）、氧合指数（OI）]、呼吸暂停发生率、通气失败率以及并发症发生率。结果：（1）观察组患儿机械通气时间、氧暴露时间、住院时间均较对照组少（P<0.05）。（2）观察组患儿进行性呼吸困难、吸气三凹征、气促改善时间均显著少于对照组（P<0.05）。（3）观察组患儿治疗72 h时的PaO₂显著高于对照组,PaCO₂和OI显著低于对照组（P<0.05）。（4）观察组呼吸暂停发生率和通气失败率为16.00%和10.00%,与对照组并无显著差异（P＞0.05）。（5）观察组术后并发症总发生率为4.00 %显著低于对照组的26.00 %（P<0.05）。结论：与NIPPV联合无创PS比较,nHFOV联合微创PS更能有效改善NRDS患儿肺通气功能,缩短机械通气时间,减少并发症。     

Intrusiefouten bij geheugenonderzoek

Extra-list intrusion errors during five trials of the eight-word list-learning task of the Amsterdam Dementia Screening Test (ADST) were investigated in 823 consecutive psychogeriatric patients (87.1% suffering from major neurocognitive disorder). Almost half of the participants (45.9%) produced one or more intrusion errors on the verbal recall test. Correct responses were lower when subjects made intrusion errors, but learning slopes did not differ between subjects who committed intrusion errors and those who did not so. Bivariate regression analyses revealed that participants who committed intrusion errors were more deficient on measures of eight-word recognition memory, delayed visual recognition and tests of executive control (the Behavioral Dyscontrol Scale and the ADST-Graphical Sequences as measures of response inhibition). Using hierarchical multiple regression, only free recall and delayed visual recognition retained an independent effect in the association with intrusion errors, such that deficient scores on tests of episodic memory were sufficient to explain the occurrence of intrusion errors. Measures of inhibitory control did not add significantly to the explanation of intrusion errors in free recall, which makes insufficient strength of memory traces rather than a primary deficit in inhibition the preferred account for intrusion errors in free recall.     

Neuromodulation Integrating rTMS and Neurofeedback for the Treatment of Autism Spectrum Disorder: An Exploratory Study

Autism spectrum disorder (ASD) is a pervasive developmental disorder characterized by deficits in social interaction, language, stereotyped behaviors, and restricted range of interests. In previous studies low frequency repetitive transcranial magnetic stimulation (rTMS) has been used, with positive behavioral and electrophysiological results, for the experimental treatment in ASD. In this study we combined prefrontal rTMS sessions with electroencephalographic (EEG) neurofeedback (NFB) to prolong and reinforce TMS-induced EEG changes. The pilot trial recruited 42 children with ASD (~14.5 years). Outcome measures included behavioral evaluations and reaction time test with event-related potential (ERP) recording. For the main goal of this exploratory study we used rTMS-neurofeedback combination (TMS-NFB, N = 20) and waitlist (WTL, N = 22) groups to examine effects of 18 sessions of integrated rTMS-NFB treatment or wait period) on behavioral responses, stimulus and response-locked ERPs, and other functional and clinical outcomes. The underlying hypothesis was that combined TMS-NFB will improve executive functions in autistic patients as compared to the WTL group. Behavioral and ERP outcomes were collected in pre- and post-treatment tests in both groups. Results of the study supported our hypothesis by demonstration of positive effects of combined TMS-NFB neurotherapy in active treatment group as compared to control WTL group, as the TMS-NFB group showed significant improvements in behavioral and functional outcomes as compared to the WTL group.     

Reducing Specific Phobia/Fear in Young People with Autism Spectrum Disorders (ASDs) through a Virtual Reality Environment Intervention

Anxiety is common in children with autism spectrum disorders (ASD), with specific fears and phobias one of the most frequent subtypes. Specific fears and phobias can have a serious impact on young people with ASD and their families. In this study we developed and evaluated a unique treatment combining cognitive behaviour therapy (CBT) with graduated exposure in a virtual reality environment (VRE). Nine verbally fluent boys with an ASD diagnosis and no reported learning disability, aged 7 to 13 years old, were recruited. Each had anxiety around a specific situation (e.g. crowded buses) or stimulus (e.g. pigeons). An individualised scene was recreated in our ‘wrap-around’ VRE. In the VRE participants were coached by a psychologist in cognitive and behavioural techniques (e.g. relaxation and breathing exercises) while the exposure to the phobia/fear stimulus was gradually increased as the child felt ready. Each child received four 20–30 minute sessions. After participating in the study, eight of the nine children were able to tackle their phobia situation. Four of the participants completely overcame their phobia. Treatment effects were maintained at 12 months. These results provide evidence that CBT with VRE can be a highly effective treatment for specific phobia/fear for some young people with ASD.

Trial Registration

Controlled-Trials.com ISRCTN58483069.     

Impaired structural connectivity of socio-emotional circuits in autism spectrum disorders: a diffusion tensor imaging study

Background

Abnormal white matter development may disrupt integration within neural circuits, causing particular impairments in higher-order behaviours. In autism spectrum disorders (ASDs), white matter alterations may contribute to characteristic deficits in complex socio-emotional and communication domains. Here, we used diffusion tensor imaging (DTI) and tract based spatial statistics (TBSS) to evaluate white matter microstructure in ASD.

Methods/Principal Findings

DTI scans were acquired for 19 children and adolescents with ASD (∼8–18 years; mean 12.4±3.1) and 16 age and IQ matched controls (∼8–18 years; mean 12.3±3.6) on a 3T MRI system. DTI values for fractional anisotropy, mean diffusivity, radial diffusivity and axial diffusivity, were measured. Age by group interactions for global and voxel-wise white matter indices were examined. Voxel-wise analyses comparing ASD with controls in: (i) the full cohort (ii), children only (≤12 yrs.), and (iii) adolescents only (>12 yrs.) were performed, followed by tract-specific comparisons. Significant age-by-group interactions on global DTI indices were found for all three diffusivity measures, but not for fractional anisotropy. Voxel-wise analyses revealed prominent diffusion measure differences in ASD children but not adolescents, when compared to healthy controls. Widespread increases in mean and radial diffusivity in ASD children were prominent in frontal white matter voxels. Follow-up tract-specific analyses highlighted disruption to pathways integrating frontal, temporal, and occipital structures involved in socio-emotional processing.

Conclusions/Significance

Our findings highlight disruption of neural circuitry in ASD, particularly in those white matter tracts that integrate the complex socio-emotional processing that is impaired in this disorder.     

Effect of L-Carnosine in children with autism spectrum disorders: a systematic review and meta-analysis of randomised controlled trials

Autism spectrum disorders (ASD) are an emerging health problem worldwide. So far, no definite cure for ASD exists. L-Carnosine is an amino acid containing β-alanine and L-histidine which has been proposed to have neuroprotective, antioxidant and anti-convulsive properties that may benefit affected children with this disorder. This review aimed to assess the effect of L-Carnosine in the management of ASD in children. We systematically reviewed randomised controlled trials (RCTs) which documented the effect of L-Carnosine in children with ASD. A literature search was performed in PubMed, Cochrane Library, Google Scholar, ClinicalTrials.gov, Clinical Trial Registry-India databases from inception to December 20, 2020. Articles were selected based on pre-set inclusion/exclusion criteria. The primary outcomes were changes in social, communication and behavioural responses and the secondary outcomes were improvement in sleep disorders, gastrointestinal problems, oxidative stress markers and adverse effects. Jadad scale was used to assess the quality of RCTs and modified Cochrane risk of bias tool was used to check the risk of bias of the included studies. The meta-analysis was reported based on the fixed-effects model. Four double-blinded, placebo-controlled, RCTs and one open label trial with a total of 215 participants were selected for the review. All the trials were methodological of high quality according to the Jadad scale. The modified Cochrane risk of bias tool showed a low to high risk of bias. Results from the meta-analysis of three studies showed no significant difference between L-Carnosine and placebo groups in the Gilliam autism rating scale (GARS) (MD = − 2.57; 95% CI − 10.30, 5.16, p = 0.52) and in its socialisation (MD = − 1.51; 95% CI − 6.16, 3.14, p = 0.53), behaviour (MD = − 0.48; 95% CI − 4.82, 3.87, p = 0.83) and communication (MD = − 3.94; 95% CI − 10.00, 2.11, p = 0.20) subscales as well as the childhood autism rating scale (CARS) (MD = − 0.88; 95% CI − 6.96, 5.20; p = 0.78). Current data do not support the use of L-Carnosine in the management of children with ASD due to a low number of studies and sample size available. Further studies are warranted to know the effect of L-Carnosine for ASD management.

     

The reliability of jump kinematics and kinetics in children of different maturity status

The purpose of this study was to determine the reliability of eccentric (ECC) and concentric (CON) kinematic and kinetic variables thought to be critical to jump performance during bilateral vertical countermovement jump (VCMJ) and horizontal countermovement jump (HCMJ) across children of different maturity status. Forty-two athletic male and female participants between 9 and 16 years of age were divided into 3 maturity groups according to peak height velocity (PHV) offset (Post-PHV, At-PHV, and Pre-PHV) and percent of predicted adult stature. All the participants performed 3 VCMJ and HCMJ trials and the kinematics, and kinetics of these jumps were measured via a force plate over 3 testing sessions. In both jumps, vertical CON mean and peak power and jump height or distance were the most reliable measures across all groups (change in the mean [CM] = -5.4 to 6.2%; coefficient of variation [CV] = 2.1-9.4%; Intraclass correlation coefficient [ICC] = 0.82-0.98), whereas vertical ECC mean power was the only ECC variable with acceptable reliability for both jumps (CM = -0.7 to 10.1%; CV = 5.2-15.6%; ICC = 0.74-0.97). A less mature state was "likely" to "very likely" to reduce the reliability of the HCMJ ECC kinetics and kinematics. These findings suggested that movement variability is associated with the ECC phase of CMJs, especially in Pre-PHV during the HCMJ. Vertical CON mean and peak power and ECC mean power were deemed reliable and appropriate to be used in children as indicators of jump and stretch-shortening cycle performance.     

Prevalence and Correlates of Elopement in a Nationally Representative Sample of Children with Developmental Disabilities in the United States

Despite increased awareness and concern about children with developmental disabilities wandering away from adult supervision, there is a paucity of research about elopement. This is the first study to examine and report the prevalence and correlates of elopement in a nationally representative sample of school-age children in the United States with an autism spectrum disorder (ASD) and/or cognitive impairment. Data were obtained from the CDC''s "Pathways" Survey, a follow-up telephone survey of the parents of 4,032 children with a developmental condition. 3,518 children that had ASD, intellectual disability (ID), and/or developmental delay (DD) at the time of survey administration were included for analysis. Children were divided into three condition groups: ASD-only; ID/DD-only; ASD+ID/DD. Logistic regression analyses were used to compare the prevalence of elopement and rates of preventive measure use (barriers and/or electronic devices) across condition groups, and to examine the clinical and demographic correlates of elopement. T-tests were also performed to compare scores on the Children''s Social Behavior Questionnaire (CSBQ) between wanderers and non-wanderers. Overall, 26.7% of children had reportedly eloped within the previous year, most commonly from public places. Children with ASD-only and ASD+ID/DD were more likely to have eloped than those with ID/DD-only. Across all groups, wanderers scored higher than non-wanderers on five out of six CSBQ subscales; they were more likely not to realize when there is danger, to have difficulty distinguishing between strangers and familiar people, to show sudden mood changes, to over-react to everything/everyone, to get angry quickly, to get lost easily, and to panic in new situations or if change occurs. Even after controlling for elopement history, parents of children in the ASD+ID/DD group were more likely than those in the other condition groups to report using physical or electronic measures to prevent wandering.     

Di-(2-ethylhexyl) phthalate and autism spectrum disorders

ASDs (autism spectrum disorders) are a complex group of neurodevelopment disorders, still poorly understood, steadily rising in frequency and treatment refractory. Extensive research has been so far unable to explain the aetiology of this condition, whereas a growing body of evidence suggests the involvement of environmental factors. Phthalates, given their extensive use and their persistence, are ubiquitous environmental contaminants. They are EDs (endocrine disruptors) suspected to interfere with neurodevelopment. Therefore they represent interesting candidate risk factors for ASD pathogenesis. The aim of this study was to evaluate the levels of the primary and secondary metabolites of DEHP [di-(2-ethylhexyl) phthalate] in children with ASD. A total of 48 children with ASD (male: 36, female: 12; mean age: 11±5 years) and age- and sex-comparable 45 HCs (healthy controls; male: 25, female: 20; mean age: 12±5 years) were enrolled. A diagnostic methodology, based on the determination of urinary concentrations of DEHP metabolites by HPLC-ESI-MS (HPLC electrospray ionization MS), was applied to urine spot samples. MEHP [mono-(2-ethylhexenyl) 1,2-benzenedicarboxylate], 6-OH-MEHP [mono-(2-ethyl-6-hydroxyhexyl) 1,2-benzenedicarboxylate], 5-OH-MEHP [mono-(2-ethyl-5-hydroxyhexyl) 1,2-benzenedicarboxylate] and 5-oxo-MEHP [mono-(2-ethyl-5-oxohexyl) 1,2-benzenedicarboxylate] were measured and compared with unequivocally characterized, pure synthetic compounds (>98%) taken as standard. In ASD patients, significant increase in 5-OH-MEHP (52.1%, median 0.18) and 5-oxo-MEHP (46.0%, median 0.096) urinary concentrations were detected, with a significant positive correlation between 5-OH-MEHP and 5-oxo-MEHP (r_s = 0.668, P<0.0001). The fully oxidized form 5-oxo-MEHP showed 91.1% specificity in identifying patients with ASDs. Our findings demonstrate for the first time an association between phthalates exposure and ASDs, thus suggesting a previously unrecognized role for these ubiquitous environmental contaminants in the pathogenesis of autism.     

The Incremental Validity of Lumbar Surface EMG, Behavioral Observation, and a Symptom Checklist in the Assessment of Patients with Chronic Low-Back Pain

This study evaluated the comparative ability of lumbar surface EMG, behavioral observation, and a symptom checklist to correctly classify three groups of participants, (1) 18 patients with chronic low-back pain (CLBP), demonstrating excessive and/or anatomically inconsistent motor, sensory, and tenderness responses during a neurological examination, (2) 33 patients with CLBP exhibiting few or no inconsistent responses, and (3) 30 healthy matched controls. Discriminant analyses were used to develop predictive models. Correct classification rates for the individual assessments and all combinations of assessments were contrasted. Each modality predicted group membership significantly better than weighted chance (23%), with the symptom checklist approach having the highest individual correct classification rate (64%). The best combination of modalities was the symptom checklist and lumbar surface EMG (70% correct classification rate). The sensitivity and specificity of the individual assessments and all combinations of assessments are also presented.     

Concurrent Relations between Face Scanning and Language: A Cross-Syndrome Infant Study

Typically developing (TD) infants enhance their learning of spoken language by observing speakers’ mouth movements. Given the fact that word learning is seriously delayed in most children with neurodevelopmental disorders, we hypothesized that this delay partly results from differences in visual face scanning, e.g., focusing attention away from the mouth. To test this hypothesis, we used an eye tracker to measure visual attention in 95 infants and toddlers with Down syndrome (DS), fragile X syndrome (FXS), and Williams syndrome (WS), and compared their data to 25 chronological- and mental-age matched 16-month-old TD controls. We presented participants with two talking faces (one on each side of the screen) and a sound (/ga/). One face (the congruent face) mouthed the syllable that the participants could hear (i.e., /ga/), while the other face (the incongruent face) mouthed a different syllable (/ba/) from the one they could hear. As expected, we found that TD children with a relatively large vocabulary made more fixations to the mouth region of the incongruent face than elsewhere. However, toddlers with FXS or WS who had a relatively large receptive vocabulary made more fixations to the eyes (rather than the mouth) of the incongruent face. In DS, by contrast, fixations to the speaker’s overall face (rather than to her eyes or mouth) predicted vocabulary size. These findings suggest that, at some point in development, different processes or strategies relating to visual attention are involved in language acquisition in DS, FXS, and WS. This knowledge may help further explain why language is delayed in children with neurodevelopmental disorders. It also raises the possibility that syndrome-specific interventions should include an early focus on efficient face-scanning behaviour.     

Behavioral,Cognitive, and Motor Preparation Deficits in a Visual Cued Spatial Attention Task in Autism Spectrum Disorder

Abnormalities in motor skills have been regarded as part of the symptomatology characterizing autism spectrum disorder (ASD). It has been estimated that 80 % of subjects with autism display “motor dyspraxia” or clumsiness that are not readily identified in a routine neurological examination. In this study we used behavioral measures, event-related potentials (ERP), and lateralized readiness potential (LRP) to study cognitive and motor preparation deficits contributing to the dyspraxia of autism. A modified Posner cueing task was used to analyze motor preparation abnormalities in children with autism and in typically developing children (N = 30/per group). In this task, subjects engage in preparing motor response based on a visual cue, and then execute a motor movement based on the subsequent imperative stimulus. The experimental conditions, such as the validity of the cue and the spatial location of the target stimuli were manipulated to influence motor response selection, preparation, and execution. Reaction time and accuracy benefited from validly cued targets in both groups, while main effects of target spatial position were more obvious in the autism group. The main ERP findings were prolonged and more negative early frontal potentials in the ASD in incongruent trials in both types of spatial location. The LRP amplitude was larger in incongruent trials and had stronger effect in the children with ASD. These effects were better expressed at the earlier stages of LRP, specifically those related to response selection, and showed difficulties at the cognitive phase of stimulus processing rather that at the motor execution stage. The LRP measures at different stages reflect the chronology of cognitive aspects of movement preparation and are sensitive to manipulations of cue correctness, thus representing very useful biomarker in autism dyspraxia research. Future studies may use more advance and diverse manipulations of movement preparation demands in testing more refined specifics of dyspraxia symptoms to investigate functional connectivity abnormalities underlying motor skills deficits in autism.     

Neuropsychological consequences of volatile substance abuse: a population based study of secondary school pupils.

OBJECTIVE--To examine the effects of volatile substance abuse on neuropsychological functioning. DESIGN--A sample of index children and matched controls were identified by a two stage procedure. Firstly, over 5000 secondary school pupils completed a screening questionnaire, and, secondly, a sample of those who acknowledged volatile substance abuse and a matched sample of those who denied the practice were assessed in detail by means of (a) individually conducted interviews and (b) toxicological examination of breath samples (to exclude those intoxicated at the time of testing). SETTING--16 Local education authority secondary schools in London. SUBJECTS--160 Pupils aged 13-16: 80 index children who had abused volatile substances to the point of intoxication at least once (confirmed by interview) and 80 controls (confirmed by interview) matched for school year, sex, and ethnic background. MEASUREMENTS AND MAIN RESULTS--Neuropsychological functioning tests provided 35 main outcome measures and were administered blind. Data on educational test performance before substance abuse began were obtained retrospectively. Information on potentially confounding social factors, such as number of siblings, tenure of housing, and parents'' socioeconomic and employment state was also obtained. The index children performed significantly less well than the controls in tests of vocabulary, verbal intelligence quotient, full scale intelligence quotient, and a measure of impulsivity. When background social disadvantage was taken into account these differences were no longer significant. There were no significant associations between performance on psychological testing and frequency of abuse, and relations with other aspects of the children''s history of abuse were generally weak or unsystematic. Comparisons between the results of these tests and of educational tests taken before substance abuse produced equivocal findings. CONCLUSION--Volatile substance abuse, as commonly practised by secondary school pupils, is unlikely to result in neuropsychological impairment.     

A multi-centre randomized controlled trial of rehabilitation aimed at improving outdoor mobility for people after stroke: study protocol for a randomized controlled trial

ABSTRACT: BACKGROUND: Up to 42% of all stroke patients do not get out of the house as much as they would like. This can impede a person's quality of life. This study is testing the clinical effectiveness and cost effectiveness of a new outdoor mobility rehabilitation intervention by comparing it to usual care. METHODS: Multi-centre parallel group individually randomised controlled trial. At least 506 participants will be recruited through 15 primary and secondary care settings and will be eligible if they are over 18 years of age, have had a stroke and wish to get out of the house more often. Participants are being randomly allocated to either the intervention group or the control group. Intervention group participants receive up to 12 rehabilitation outdoor mobility sessions over up to 4 months. The main component of the intervention is repeated practice of outdoor mobility with a therapist. Control group participants are receiving the usual intervention for outdoor mobility limitations: verbal advice and provision of leaflets provided over one session. Outcome measures are being collected using postal questionnaires, travel calendars and by independent assessors. The primary outcome measure is the Social Function domain of the SF36v2 quality of life assessment six months after recruitment. The secondary outcome measures include: functional ability, mobility, the number of journeys (monthly travel diaries), satisfaction with outdoor mobility, mood, health-related quality of life, resource use of health and social care. Carer mood is also being collected. The mean Social Function score of the SF-36v2 will be compared between treatment arms using a multiple membership form of mixed effects multiple regression analysis adjusting for centre (as a fixed effect), age and baseline Social Function score as covariates and therapist as a multiple membership random effect. Regression coefficients and 95% confidence intervals will be presented. DISCUSSION: This study protocol describes a pragmatic randomised controlled trial that will hopefully provide robust evidence of the benefit of outdoor mobility interventions after stroke for clinicians working in the community. The results will be available towards the end of 2012.